Woo Minji, Kim Mijeong, Noh Jeong Sook, Park Chan Hum, Song Yeong Ok
Department of Food Science and Nutrition, Kimchi Research Institute, Pusan National University, 2, Busandaehak-ro 63 beon-gil, Geumjeong-gu, Busan 46241, Korea.
Department of Food Science and Nutrition, Tongmyong University, Busan 48520, Korea.
Nutr Res Pract. 2017 Dec;11(6):445-451. doi: 10.4162/nrp.2017.11.6.445. Epub 2017 Sep 25.
BACKGROUND/OBJECTIVES: Endoplasmic reticulum (ER) stress is positively associated with atherosclerosis via elevating macrophage cell death and plaque formation, in which oxidative stress plays a pivotal role. Antioxidative, lipid-lowering, and anti-atherogenic effects of kimchi, a Korean fermented vegetable, have been established, wherein capsaicin, ascorbic acid, quercetin, 3-(4'-hydroxyl-3',5'-dimethoxyphenyl)propionic acid, and lactic acids were identified. In this study, mechanisms of action of kimchi methanol extracts (KME) on fatty streak formation via suppression of ER stress and apoptosis in aorta were examined in low-density lipoprotein receptor knockout mice.
Mice fed a high cholesterol diet with an oral administration of KME (KME group, 200 mg·kg-bw·day) or distilled water (control group) for 8 weeks (n = 20 for group). Plasma lipid and oxidative stress levels were evaluated. Protein expression was measured by western blot assay. Fatty streak lesion size and the degree of apoptosis were examined in the aorta.
Compared to the control group, in the KME group, plasma lipids levels were decreased and oxidative stress was alleviated ( < 0.05). Protein expression levels of nuclear factor (erythroid-derived 2)-like 2-mediated antioxidants in aorta were increased whereas those for ER stress markers, glucose regulated protein 78, phospho-protein kinase RNA-like ER kinase, phospho-eukaryotic initiation factor 2 subunit α, X-box binding protein 1, and C/EBP homologous protein were decreased in the KME group ( < 0.05). Moreover, apoptosis was suppressed via downregulation of phospho-c-Jun N-terminal kinase, bcl-2-associated X protein, caspases-9, and -3 with a concomitant upregulation of anti-apoptotic protein, B-cell lymphoma 2 ( < 0.05). Fatty streak lesion size was reduced and the degree of apoptosis was less severe in the KME group ( < 0.05).
In conclusion, antioxidant activity of KME might prevent fatty streak formation through, in part, inhibition of ER stress and apoptosis in aortic sinus where macrophages are harbored.
背景/目的:内质网(ER)应激通过增加巨噬细胞死亡和斑块形成与动脉粥样硬化呈正相关,其中氧化应激起关键作用。韩国发酵蔬菜泡菜具有抗氧化、降血脂和抗动脉粥样硬化作用,已鉴定出其中含有辣椒素、抗坏血酸、槲皮素、3-(4'-羟基-3',5'-二甲氧基苯基)丙酸和乳酸。本研究在低密度脂蛋白受体敲除小鼠中研究了泡菜甲醇提取物(KME)通过抑制主动脉内质网应激和细胞凋亡对脂肪条纹形成的作用机制。
给小鼠喂食高胆固醇饮食,口服KME(KME组,200mg·kg体重·天)或蒸馏水(对照组)8周(每组n = 20)。评估血浆脂质和氧化应激水平。通过蛋白质印迹法测量蛋白质表达。检查主动脉中脂肪条纹病变大小和细胞凋亡程度。
与对照组相比,KME组血浆脂质水平降低,氧化应激减轻(P < 0.05)。主动脉中核因子(红细胞衍生2)样2介导的抗氧化剂的蛋白质表达水平增加,而KME组内质网应激标志物葡萄糖调节蛋白78、磷酸化蛋白激酶RNA样内质网激酶、磷酸化真核起始因子2亚基α、X盒结合蛋白1和C/EBP同源蛋白的表达水平降低(P < 0.05)。此外,通过下调磷酸化c-Jun N末端激酶、bcl-2相关X蛋白、半胱天冬酶-9和-3以及同时上调抗凋亡蛋白B细胞淋巴瘤2抑制细胞凋亡(P < 0.05)。KME组脂肪条纹病变大小减小,细胞凋亡程度较轻(P < 0.05)。
总之,KME的抗氧化活性可能部分通过抑制巨噬细胞所在的主动脉窦中的内质网应激和细胞凋亡来预防脂肪条纹形成。